The retinal pigment epithelium (RPE) is the pigmented cell layer just outside the neurosensory retina. This layer of cells nourishes retinal visual cells, and is attached to the underlying choroid (the layer of blood vessels behind the retina) and overlying retinal visual cells. The RPE acts as a filter to determine what nutrients reach the retina from the choroid. Additionally, the RPE provides insulation between the retina and the choroid. Breakdown of the RPE interferes with the metabolism of the retina, causing thinning of the retina. Thinning of the retina can have serious consequences. For example, thinning of the retina may cause “dry” macular degeneration and may also lead to the inappropriate blood vessel formation that can cause “wet” macular degeneration).
Given the importance of the RPE in maintaining visual and retinal health, there have been significant efforts in studying the RPE and in developing methodologies for producing RPE cells in vitro. RPE cells produced in vitro could be used to study the developments of the RPE, to identify factors that cause the RPE to breakdown, or to identify agents that can be used to stimulate repair of endogenous RPE cells. Additionally, RPE cells produced in vitro could themselves be used as a therapy for replacing or restoring all or a portion of a patient's damaged RPE cells. When used in this manner, RPE cells may provide an approach to treat macular degeneration, as well as other diseases and conditions caused, in whole or in part, by damage to the RPE.
The use of RPE cells produced in vitro for screening or as a therapeutic relies on methods that can be used to produce large numbers of RPE cells in a systematic, directed manner. Such systematized differentiation methods would provide significant advantages over previous schemes based on, for example, spontaneous differentiation of RPE cells from transformed cell lines or other sources.